(2R)-2-[2-[(5R,6R,7S,9R,11R,16R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid | 116355-83-0

• 物质功能分类: 分析化学 - 标准品
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-[2-[(5R,6R,7S,9R,11R,16R,18S,19S)-19-amino-6-[(3R)-3,4-dicarboxybutanoyl]oxy-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid
• CAS: 116355-83-0
• 化学式: C₃₄H₅₉NO₁₅
• 分子量: 721.8
• InChiKey: UVBUBMSSQKOIBE-WLSQKSOISA-N

物化性质

• 熔点：
  >60oC
• 沸点：
  713.81°C (rough estimate)
• 密度：
  1.2207 (rough estimate)
• 闪点：
  6 °C
• 溶解度：
  溶于水（高达 25 mg/ml）。
• 颜色/状态：
  Powder

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  50
• 可旋转键数：
  31
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  289
• 氢给体数：
  8
• 氢受体数：
  16

ADMET

毒理性

• 毒性总结

识别：伏马毒素B1是伏马毒素中最普遍的一种，由真菌串珠镰刀菌和其他镰刀菌属产生。纯净物质是一种白色吸湿性粉末，可溶于水、乙腈-水和甲醇。该物质在食品加工温度和光照下稳定。伏马毒素B1是与玉米相关的最常见的真菌代谢物。当天气条件有利于玉米穗腐时，玉米中会显著积累。人类暴露：没有与这种化合物相关的急性毒性的确认记录。可用的相关性研究表明，饮食暴露与食管癌之间存在关联。其他研究对于伏马毒素B1的潜在致癌性尚无定论。动物/植物研究：伏马毒素B1对所有测试的动物物种（包括小鼠、大鼠、马科动物、猪、兔子和非人灵长类动物）都具有肝脏毒性。除了叙利亚仓鼠外，只有在母体毒性同时或之后才会观察到胚胎毒性或致畸性。伏马毒素对猪、大鼠、羊、小鼠和兔子具有肾脏毒性。在大鼠和兔子中，肾脏毒性发生在低于肝脏毒性的剂量下。伏马毒素已知会导致马脑白质病和猪肺水肿综合征。对某一品系的大鼠具有肝脏致癌性，对另一品系具有肾脏致癌性。伏马毒素B1是新型鞘脂代谢的特异性抑制剂。这种化合物抑制细胞生长，并在动物、植物和一些酵母（如酿酒酵母）中导致自由鞘脂基的积累和脂质代谢的改变。它没有在大肠杆菌中诱导基因突变，也没有在原代大鼠肝细胞中诱导非计划性DNA合成，但在低浓度下诱导了剂量依赖性的染色体畸变增加。这种化合物具有植物毒性，损害细胞膜并减少叶绿素合成。根据使用猪、产蛋鸡和狒狒的研究，当口服给药时，这种化合物吸收不良，并且迅速从血浆或循环中消除并在粪便中回收；胆汁排泄很重要；在一些动物中，肠肝循环很重要。少量通过尿液排出，有些保留在肝脏和肾脏中。

IDENTIFICATION: Fumonisin B1 is the most prevalent of the fumonisins and produced by the fungus Fusarium moniliforme and other F. species. The pure substance is a white hygroscopic powder and is soluble in water, acetonitrile-water and methanol. The material is stable at food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with maize. Significant accumulation in maize occurs when weather conditions favor kernel rot. HUMAN EXPOSURE: There are no confirmed records of acute toxicity associated with this compound. Available correlation studies suggest a link between dietary exposure and esophageal cancer. Other studies are inconclusive as to the potential carcinogenicity of Fumonisin B1. ANIMAL/PLANT STUDIES: Fumonisin B1 is hepatotoxic in all animal species tested including mice, rats, equids, pigs, rabbits and non-human primates. With the exception of Syrian hamsters, embryotoxicity or teratogenicity is only observed concurrent with or subsequent to maternal toxicity. Fumonisins are nephrotoxic in pigs, rats, sheep, mice and rabbits. In rats and rabbits, renal toxicity occurs at lower doses than hepatotoxicity. The fumonisins are known to cause equine leukoencephalomalacia and porcine pulmonary edema syndrome. It is hepatocarcinogenic to male rats in one strain and nephrocarcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid metabolism. This compound inhibits cell growth and causes accumulation of free sphingoid bases and alteration of lipid metabolism in animals, plants and in some yeasts such as Saccharomyces cerevisae. It did not induce gene mutations in bacteria or unscheduled DNA synthesis in primary rat hepatocytes, but induced a dose dependent increase in chromosomal aberrations at low concentrations. This compound is phytotoxic, damages cell membranes and reduces chlorophyll synthesis. This compound is poorly absorbed when dosed orally based on studies using pigs, laying hens and Vervet monkeys and it is rapidly eliminated from the plasma or circulation and recovered in the feces; biliary excretion is important; enterohepatic cycling is important in some animals. Small amounts are excreted in the urine, and some is retained in the liver and kidney.[

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于来自串珠镰刀菌的毒素在人类中的致癌性，证据不足。对于含有大量伏马毒素的串珠镰刀菌培养物在实验动物中的致癌性，有充分的证据。对于伏马毒素B1在实验动物中的致癌性，有有限的证据。总体评估：来自串珠镰刀菌的毒素可能对人类具有致癌性（2B组）。/来自串珠镰刀菌的毒素/

Evaluation: There is inadequate evidence in humans for the carcinogenicity of toxins derived from Fusarium moniliforme. There is sufficient evidence in experimental animals for the carcinogenicity of cultures of Fusarium moniliforme that contain significant amounts of fumonisins. There is limited evidence in experimental animals for the carcinogenicity of fumonisin B1. Overall evaluation: Toxins derived from Fusarium moniliforme are possibly carcinogenic to humans (Group 2B). /Toxins derived from Fusarium moniliforme/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：伏马毒素B1

IARC Carcinogenic Agent:Fumonisin B1

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第82卷：（2002年）一些传统草药药物，一些霉菌毒素，萘和苯乙烯

IARC Monographs:Volume 82: (2002) Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

Fumonisin B1（FB1）是 Sheldon 镰刀菌产生的镰刀菌素类次级代谢物中的主要化合物，与一些人类和动物疾病有关。在大鼠腹膜内给药（7.5 mg/kg）后，FB1 被迅速吸收，并在注射后20分钟内达到血浆中的最高浓度。此后，它从血浆中迅速清除，表现出符合单室模型的单指数消除阶段，半衰期为18分钟。收集24小时和48小时的尿液样本表明，只有16%的给药剂量未在尿液中代谢排出，且全部在给药后第一个24小时内排出。与此相反，通过灌胃给予相似剂量的FB1，在尿液中仅回收了0.4%的FB1。

Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

Fumonisin B1（FB1），是一种由真菌Fusarium moniliforme Sheldon产生的有毒和致癌的次级代谢产物，可以通过静脉注射或灌胃的方式给予黑猩猩（Cercopithecus aethiops）。通过静脉注射给两只雌性黑猩猩的FB1迅速从血浆中消除，消除阶段的平均半衰期为40分钟。在给药后5天内对尿液和粪便的分析显示，平均47%的剂量以FB1及其水解类似物形式回收。两只雌性黑猩猩通过一次灌胃给予14C标记的FB1。在随后的3天内，放射性物质的粪便排泄平均占给药剂量的61%，尿液排泄占1.2%。从骨骼肌（1%）、肝脏（0.4%）、大脑（0.2%）、肾脏、心脏、血浆、红细胞和胆汁（每个0.1%）中回收到低水平的残留放射性物质，而肠内容物占放射性剂量的另外12%。总的来说，76%的给药放射性物质被回收。对粪便、肠内容物和尿液的分析表明，这些样本中的超过90%的放射性物质是由FB1及其水解产物引起的。

Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一种用于测定非人灵长类（长尾猴）粪便中伏马菌素B1（FB1）的方法已经开发出来。动物被喂食了标记有14C的FB1，通过用0.1 M乙二胺四乙酸反复提取，回收粪便中的放射性化合物。提取物在反相（C18）固相萃取柱上进行净化，然后通过o-苯基甲醛衍生化和反相高效液相色谱法测定FB1。粪便提取物中FB1的测定方法具有可重复性[2.6%相对标准偏差（RSD）]和准确性（从加标空白提取物中的回收率为93 +/- 2.9% RSD）。通过高效液相色谱和薄层色谱确认了粪便中FB1的鉴定，表明提取的放射性主要对应于FB1和一个具有与霉菌毒素相似色谱性质的新代谢物。通过质谱和核磁共振光谱鉴定出新代谢物是部分水解FB1的两个结构异构体的平衡混合物，这些异构体是通过霉菌毒素的一个酯基的水解形成的。

A method has been developed for the determination of fumonisin B1 (FB1) in the feces of non-human primates (vervet monkeys). The animals were dosed with 14C-labelled FB1, and the radioactive compounds in faeces were recovered by repeated extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned-up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The analytical method for the determination of FB1 in the fecal extracts was reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed that the radioactivity extracted corresponded mainly to FB1 and a new metabolite with chromatographic properties similar to those of the mycotoxin. The new metabolite was identified by mass spectrometry and nuclear magnetic resonance spectroscopy to be an equilibrium mixture of the two structural isomers of partially hydrolysed FB1, which are formed by hydrolysis of one of the ester groups of the mycotoxin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

真菌毒素伏马毒素B1（FB1）会引起动物的各种健康问题，而流行病学证据表明它与人类食管癌有关。我们使用隔离灌注的牛乳腺研究了FB1进入牛乳的情况。将2毫克FB1注入3个乳腺的灌注血液中，并在150分钟内测定了乳汁和灌注血清中的水平。FB1穿过了乳腺屏障进入乳汁，但浓度如此之低，对消费者来说风险可以忽略不计。

The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals, while epidemiological evidence suggests it is linked to human esophageal cancer. We investigated the carry-over of FB1 into bovine milk using the isolated perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3 udders, and milk and perfused serum levels were determined for 150 min. FB1 passed through the mammary barrier into the milk, but in such low concentrations as to present a negligible risk for consumers.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,F,T
• 危险类别码：
  R40
• 危险品运输编号：
  UN 3172
• WGK Germany：
  2,3
• RTECS号：
  TZ8350000
• 海关编码：
  29221990
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 安全说明：
  S16,S36/37

制备方法与用途

背景 伏马毒素（Fumonisin，Macrofusine）主要发生在玉米上，包括至少15种相近的毒素，其中最主要的是伏马毒素B1（Fumonisin B1，FB1）。尽管在150年前就发现伏马毒素对马有影响，正式鉴定还是在20世纪80年代中期。伏马毒素是几种镰刀菌（Fusarium moniliforme）的极性代谢产物，其基本结构是一种包含甲基和氨基的长链羟基烃链。两个羟基被酯化到两个丙-1,2,3-三羧酸上。

生物活性 Fumonisin B1 是一种由 Fusarium moniliforme 产生的霉菌毒素，是 sphingosine N-acyltransferase (ceramide synthase) 的有效抑制剂，破坏鞘脂从头生物合成。Fumonisin B1 是最丰富和最有毒的伏马菌素。

靶点 Sphingosine N-acyltransferase

体外研究 Fumonisin B1 改变了猴肾细胞中的基因表达和信号传导通路，增加了 LLC-PK1 肾细胞中鞘脂代谢的初始破坏以及鞘胺醇的积累。在大鼠星形胶质细胞中引起凋亡类型的 DNA 损伤。

类别 有毒物质

毒性分级 剧毒

急性毒性 口服-猴 TDL0: 1 毫克/公斤

可燃性危险特性 可燃，火场排出辛辣刺激烟雾

储运特性 库房低温、通风、干燥；与食品原料分开存放

灭火剂 水、二氧化碳、干粉、砂土